Testing for Treatment Compliance

At a minimum, most specimens from patients maintained on methadone should be tested for methadone and its metabolites (testing for metabolites prevents patients from simply adding methadone to a sample), which can be done efficiently and at reasonable cost. Currently, no precise test measures buprenorphine in a patient specimen, although it can be detected in urine, blood, or hair by gas chromatography/mass spectrometry (GC/MS) (Lisi et al. 1997; Vincent et al. 1999) and, as reported by Cirimele and colleagues (2003), by enzyme-linked immunosorbent assay in urine. Until new, commercially available tests are developed, drug testing of patients receiving buprenorphine primarily should be to detect substances of abuse. No reagent is commercially available at reasonable cost to test any specimen type for levo-alpha acetyl methadol (LAAM), although LAAM can be detected in urine by thin-layer chromatography (TLC) and GC/MS (Moody et al. 1995). Therefore, the consensus panel recommends direct monitoring of patients receiving LAAM (American Association for the Treatment of Opioid Dependence, n.d.), assuming that its availability continues (see chapter 3).

Testing for Substances of Abuse

At a minimum, OTPs should test for opioids, cocaine, and benzodiazepines and consider testing for other drugs (e.g., methamphetamine), depending on local substance use patterns. OTP administrators should decide whether to test routinely for alcohol and marijuana or only as needed. Because of the increased depressive effects of alcohol combined with an opioid such as methadone, it is important for OTPs to avoid providing opioid medication to patients who are intoxicated with alcohol. However, no standard cutoff scores for permissible alcohol levels exist across OTPs. Because urine tests for alcohol are highly variable (Warner 2003), breath and blood tests are more useful in OTPs to determine the presence or degree of acute alcohol intoxication. Because breath tests are much simpler and faster and are less invasive than blood tests, they are the most common alcohol testing method used in OTPs.

Exhibit 9-1 summarizes necessary minimum (or cutoff) concentrations for detection of some illicit and prescription drugs in urine, as well as their reliable detection times for both initial patient testing and confirmation of positive results.

Urine Drug Testing

Despite its limitations, urine drug testing is dominant in OTPs because obtaining specimens is relatively easy (Moolchan et al. 2001) and testing is affordable. In addition, the technique is well studied, has been in use for a long time, and has well-established cutoff levels and other laboratory guidelines (Cone and Preston 2002). According to one survey (Jones et al. 1994), most patients accept urine testing in an OTP although many do not like it. Concerns usually relate to the specimen collection process or the sensitivity and specificity of results, as well as the possibility of tampering, the need to preserve patient privacy and dignity, risks of collection to staff, and the possibility that substance interactions may confound results.

A patient's physical condition can affect test sensitivity and specificity. Urine testing is not feasible for patients with renal failure (e.g., those on dialysis) or other bladder control impairments. George and Braithwaite (1999) found that variations in metabolism and excretion could affect urine concentrations of methadone or its metabolites. Moolchan and colleagues (2001) noted that renal methadone clearance varies for subjects with certain medical conditions (e.g., renal disease) and those taking other prescribed or illicit drugs. As a result, urine drug tests for patients on relatively low methadone dosages may be methadone negative even though subjects have ingested medication as prescribed (i.e., a false negative result). Furthermore, individuals with paruresis (“shy bladder syndrome”) have a social anxiety disorder that may leave them unable to urinate under observation (Labbate 1996-1997; Vythilingum et al. 2002).

Just as some patients metabolize methadone or other treatment medications at different rates and some medications affect the metabolism of others (see chapter 3), certain medications, for example, HIV medications, change the metabolism of addiction medications and can affect drug test results. OTP staff members should remain current on these interactions as more data become available (see De Maria 2003). A Web site that provides up-to-date information on the pharmacokinetics of methadone and HIV medications is at www.hiv-druginteractions.org.

Baker and colleagues (1995) found similar urine drug test results regardless of whether patients were notified of tests in advance. In that study, some patients stated that unannounced urine tests deterred them from substance use, but 53 percent said it did not. Contrary to assumptions by some providers that substance abuse is more likely over weekends (presumably resulting in more positive drug tests on Mondays), Compton and colleagues (1996) found that urine drug test results did not vary by day of the week.

Oral-Fluid Drug Testing

Oral-fluid drug testing is an alternative to urine drug testing in OTPs that is approved by SAMHSA (Clark 2003; for a recent review of oral-fluid drug testing, see Kintz and Samyn 2002), but only when a qualified offsite laboratory performs the specimen analysis. According to SAMHSA's interim guidance on the use of oral-fluid testing in OTPs, sent to OTPs in July 2003 (Clark 2003), offsite drug testing using oral fluid may be considered adequate for the purpose of 42 CFR, Part 8 § 12(f)(6). The choice of drug-testing methodology is an informed medical judgment decision. It is SAMHSA's view that there is sufficient information to confirm the adequacy of oral-fluid testing in the OTP setting. CSAT noted that OTPs still must conform to State laws and regulations in this area (Clark 2003).

Many patients in OTPs react more favorably to the use of oral swabs than to observed urine collection. Researchers have confirmed other benefits of oral-fluid testing. Moore and colleagues (2001) reported that it was highly sensitive and specific for methadone and opioids of abuse and that samples could be stored or sent to a laboratory for analysis. Braithwaite and colleagues (1995) noted that oral-fluid testing ensured privacy and was less susceptible to tampering than urine testing and that specimens required little preparation.

Results of oral-fluid testing generally are similar to those obtained by urine drug testing, but differences exist, and OTP staff members should understand these differences. Concentrations of some substances are lower in saliva than in urine. Some drugs remain detectable longer in urine than in saliva. Drug residue in the oral or nasal cavity was found to contaminate saliva specimens (Swotinsky and Smith 1999). The consensus panel recommends oral-fluid testing when drug testing must be observed because it is more respectful and less invasive and observation does not require watching patients void. Oral-fluid collection requires no temperature strips or other devices to ensure that a specimen was just provided.

Blood Drug Testing

OTPs rarely if ever use blood testing routinely; most often, they use this method to monitor plasma methadone levels when necessary. Testing for the presence of methadone in serum, although more costly than urine testing, is the most accurate method currently available to determine whether other prescribed medications influence methadone metabolism or a patient is a rapid metabolizer. Serum testing is more accurate than other methods to address issues related to the effects of metabolism on methadone dosage.

Blood testing has limitations besides cost. Blood offers a smaller drug detection window than oral fluid or urine; most drugs are undetectable in blood after 12 hours (DuPont 1999). Trained personnel must obtain blood specimens. Concerns about blood-borne pathogens make routine blood testing impractical, and, as discussed in chapter 3, some medications and diseases affect methadone levels in plasma.

Sweat Drug Testing

Sweat patches usually are used as an adjunct to other forms of testing. They provide a longer specimen collection period than either urine or blood and may be less susceptible to tampering than urine. Sweat patches are tolerated well by patients and are considered less invasive and less potentially embarrassing. Taylor and colleagues (1998) found that women were more likely than men to prefer a sweat patch to urine testing. The patch has not been found to deter substance use (Taylor et al. 1998). Preston and colleagues (1999a ) compared the patch method with urine testing for detection of cocaine and found good concordance between the two methods.

Playing-card-sized, waterproof adhesive patches are available. Each patch is imprinted with a unique number to track its chain of custody. After a patch is worn for about 1 week, a laboratory can extract about 2 mL of sample to be tested. Compared with urine specimens, sweat yields higher proportions of parent drugs, such as cocaine, heroin, or marijuana. Drug use is assessed cumulatively, but uniform cutoff levels have not been established, and external contamination is a possibility (Swotinsky and Smith 1999).

Hair Drug Testing

Hair analysis provides a longer term look at drug use than other methods because hair retains drugs longer—for example, weeks or months, compared with the 2 or 3 days that cocaine or heroin is detectable in urine. Collecting hair specimens also is less invasive than urine or blood sampling. However, drawbacks include expense, possible ethnic bias (Kidwell et al. 2000), and environmental contamination. Studies of hair analysis have been hampered by poor design, small specimen size, and lack of confirmation. More research is needed.

Specimen Collection

Analytical Methods Used in Drug Testing

Knowledge gained from testing enhances the treatment process and ameliorates some regulatory concerns and issues facing OTPs. However, it is important for practitioners and State and Federal regulators to understand the limits of the drug testing and analytical methods used in most OTPs (Moolchan et al. 2001; Verebey et al. 1998).

Because of the volume and cost of urine testing, most OTPs use TLC or enzyme immunoassay (EIA) to analyze test specimens. The Enzyme Multiplied Immunoassay Technique (EMIT) is the EIA method used most often in this country because its costs are lower, it allows for short analysis time, it can be automated for large-scale samples, and it can be used on site by small programs (Hawks 1986; Manno 1986).

Immunoassays use antibodies with specific surface sites to which drugs or metabolites bind. For urine drug testing, either of two immunoassay types—radioimmunoassay (RIA) or EIA—can be used. RIA uses radioactive markers and requires an incubation period and centrifugation of the sample. EIA uses an enzyme as its marker. Currently, no commercially available EIA tests exist for LAAM, buprenorphine, or the buprenorphine-naloxone combination tablet.

EIA permits detection of extremely small quantities of substances but lacks specificity to determine which drug in a class is present (Saxon et al. 1990). For example, EIA can detect opioids but cannot distinguish between morphine (the metabolite of heroin excreted in urine), codeine, and other opioids, including those from poppy seeds used in baked goods. EIA does not distinguish oxycodone (e.g., Percodan^®, OxyContin^®). In areas where these drugs are abused, OTPs should take additional steps and use other methods to test for oxycodone. Exhibit 9-2 describes several widely available immunoassays.

Chromatographic analyses use flows of liquid or gas to separate molecules and isolate any drugs or drug metabolites in specimens. TLC, one of the oldest of these methods, is inexpensive but less accurate than EIA, and its accuracy depends on the skill of the laboratory technician (Hawks 1986). TLC can distinguish between drugs in a class (a limitation of EIA), but it also can produce false negative reports because it requires relatively large amounts of drugs in specimens before these drugs can be detected. Programs working with laboratories that use TLC should be aware that low doses of addiction treatment medication occasionally yield negative reports. When methadone is used in treatment, periodic assays for its primary metabolite, EDDP (2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine), are advised. Unlike methadone, EDDP is pH independent when excreted, so the absence of EDDP from urine may be a more accurate sign of tampering, substitution, or diversion. GC/MS is a sensitive method that can be used to confirm results from EMIT or TLC.

Frequency of Testing

Given concerns about the cost and reliability of drug tests, some OTPs limit testing and others assume that results are unreliable in many cases. Decisions about how to use drug testing require thought and balance. In addition to conforming to Federal and State regulations, the frequency of testing should be appropriate for each patient and should allow for a caring and rapid response to possible relapse. Drug tests should be performed with sufficient frequency and randomness to assist in making informed decisions about take-home privileges and responses to treatment.

For patients who continue to abuse drugs or test negative for treatment medication, the consensus panel recommends that OTPs institute more frequent, random tests. Increased testing provides greater protection to patients vulnerable to relapse because only short periods pass before a therapeutic intervention can be initiated. However, as emphasized throughout this chapter, programs should avoid making treatment decisions affecting patients' lives that are based solely on drug test reports.

SAMHSA requires eight drug tests per year for patients in maintenance treatment (42 CFR, Part 8 § 12(f)(6)). In the opinion of the consensus panel, this is a minimal requirement. The actual frequency of testing should be based on a patient's progress in treatment, and more testing should be performed earlier in treatment than later, when most patients are stabilized. Most OTPs develop policies and procedures on testing frequency that meet or exceed Federal requirements and accreditation standards to assist staff in planning treatment, assessing patient progress, and granting take-home privileges.

Some States require more frequent testing than that required by SAMHSA. Some also require that specific drug-testing methodologies or decision matrices be followed. OTPs must adhere to the more stringent of either the Federal or State regulations. In States with no specific requirements, Federal regulations are the only applicable standard, but, as previously noted, these requirements should be considered minimal and regulatory.

The consensus panel recommends at least one drug test at admission to an OTP. Onsite testing kits are available so that admission can continue while test results are pending (see “Onsite Test Analysis” below), although some States may disallow these kits. For patients in short-term detoxification, one initial drug test is required, whereas patients receiving longer term MAT are required to have initial and monthly random tests.

Laboratory Selection

The laboratory selected by an OTP to analyze patient specimens must comply with Health Insurance Portability and Accountability Act regulations (CSAT 2004b ) and the Clinical Laboratory Improvement Amendments (CLIA) (see discussion below). OTPs should understand a laboratory's analytical methods and know whether and how often the laboratory confirms positive findings, how long specimens are retained for testing, and when results are made available to OTPs. A laboratory should collaborate with an OTP regarding custody of specimens, confidentiality and reporting of results, turnaround times for results, and specimen retention for retesting. Programs also should understand a laboratory's minimum cutoff levels for determining and reporting positive results.

In a review of requirements for efficient, reliable urine testing for substances of abuse, Braithwaite and colleagues (1995) emphasized the importance of quality control in laboratories. They listed aspects of high-quality assessment, including performing analyses according to manufacturer's instructions, evaluating control samples for every analysis, participating in external quality assessment, adequately training and supervising staff, and carefully reporting results. They also recommended that laboratories analyze at least 20 to 30 specimens per week from each OTP, have a scientist with expertise in drug addiction and drug testing on staff, and report results confidentially within 2 to 3 days of specimen receipt.

Onsite Test Analysis

Onsite (also known as near-patient or point-of-care) drug test analysis can provide rapid results but may have limitations such as increased cost or reduced accuracy. Some State regulations disallow onsite test analysis. In an extensive review, D. Simpson and colleagues (1997) found that immediately available drug test results improved patient cooperation and program management. In their review of available commercial analytical methods, they found that all were rapid, reliable, and useful but required confirmation of positive results, and some lacked sensitivity, specificity, or both. A more recent review by George and Braithwaite (2002, p. 1639) concluded that onsite analytical devices for drugs of abuse were “an expensive and potentially inaccurate means to monitor patient treatment and drug abuse states.”

Onsite analysis of test specimens also requires that staff be trained in calibration of the testing device and interpretation of results. OTPs need ongoing quality assessment procedures. Analyses performed outside a laboratory setting require special facilities to ensure safety. Onsite specimen analysis also raises questions about the chain of custody, provision, stability, and storage of samples (Simpson, D., et al. 1997). However, the U.S. Department of Health and Human Services is developing guidelines for onsite analytical methods in workplace drug-testing programs, which suggests that this approach will become more common (Cone and Preston 2002). The use of onsite specimen analysis for decisionmaking may subject OTPs to the requirements of CLIA—Federal guidelines for any entity doing laboratory analysis of specimens from humans—and require these OTPs to obtain approval from their State health departments. If an OTP falls under CLIA requirements, it must register or seek a waiver to continue its own laboratory analysis of test specimens.

Exhibit 9-4 provides a list of commercial resources, manufacturers, and contact information for onsite analytical methods.

Responding to Unfavorable Drug Test Results

Patients who continue to abuse substances while receiving addiction treatment medication create concern among OTP staff members for their progress in treatment, negative perceptions of OTPs, and community concerns that may lead to regulatory actions by SAMHSA, accrediting bodies, or the U.S. Drug Enforcement Administration.

Most OTPs must review a significant number of unfavorable drug test results. Again, the consensus panel emphasizes that results should be used to explore different treatment interventions and treatment plans that will reduce and eliminate substance use and improve treatment compliance. Reports indicating substance abuse should signal the need for a medical review of medication dosage and for intensification of counseling and education aimed at preventing HIV and hepatitis transmission. Also, because of regulatory concern about medication diversion, reports indicating absence of treatment medication should be evaluated carefully. Because dose, pH, and urine concentration can limit detection of treatment medications, staff members should consider all these areas in conducting their medical reviews and deciding on a plan of action.

When patients deny substance use despite a positive laboratory result, a careful history of their prescribed or over-the-counter drug use should be obtained and discussed with a pathologist or chemist to determine whether these drugs might produce false positive results or otherwise confound tests. Whenever possible, a questionable test should be redone (if the specimen is available) and the result confirmed by another method. If this is impossible, confirmatory analysis should be performed for all subsequent tests. More accurate testing methods such as RIA or GC/MS can be used to verify laboratory reports. Specimens can be collected under direct observation, and a chain of custody can be maintained to assure a patient that every effort is being made to prevent errors and respond to his or her denial.

Confirmations of positive drug test results generally are conducted in a laboratory rather than at the OTP. D. Simpson and colleagues (1997) emphasized the need to confirm unexpected negative as well as positive results with additional analyses. Their exhaustive review concluded that TLC is a simple, inexpensive way to confirm the absence of methadone in a urine drug test, but gas chromatography is the best choice for rapid, reliable results. GC/MS usually is reserved for confirmation in cases with legal implications. High-performance liquid chromatography is an improving technology with an increasing role in testing for and confirming the presence of methadone and its metabolites, as well as other drugs.

Patient Falsification of Test Results

False negatives can occur as a result of patient falsification of drug test results or laboratory error. Braithwaite and colleagues (1995) summarized some ways in which patients tamper with or obscure the results of urine drug tests, including substituting urine from another person, diluting urine specimens, or adding other substances (such as bleach or salt) to samples.

Strategies to minimize sample falsification should be balanced by sound treatment ethics and the overall goals of the program—recovery and rehabilitation. Common strategies include

• Turning off hot water in bathrooms to prevent patients from heating specimens brought from elsewhere (although not feasible in States where other regulations prohibit this step)
• Using bathrooms within eyesight of staff to preclude use by more than one person at a time and feeling specimen containers for warmth as soon as received (freshly voided specimens should be near body temperature [37°C])
• Using temperature and adulterant strips or collection devices that include temperature strips
• Using a temperature “gun” (infrared thermometer [visit www.coleparmer.com]) to measure the temperature of urine specimens
• Using direct observation by staff of specimen collection.

The consensus panel believes that falsification is reduced when patients understand that urine test results are not used punitively to lower doses of addiction treatment medication. Continued use of drugs requires counseling, casework, medical review, and other interventions, not punishment. In the past, some OTPs reduced medication dosages as a direct result of positive drug tests although this has proved ineffective and sets up an adversarial relationship between patients and the OTP. When it is clear that interventions for substance abuse are ineffective, moving patients to a higher level of care, rather than discharging them, is warranted.

Patients should be encouraged to discuss their substance use with OTP physicians, caseworkers, or counselors and to trust them with this information. Ideally, once trust has developed, drug test results will confirm what already has been revealed in individual or group sessions. Nevertheless, some patients fear loss of take-home privileges or remain in denial about their drug use and do not disclose their noncompliance willingly; drug test results are necessary to alert OTPs to these patients' noncompliance.

False Positive and False Negative Drug-Testing Results

Numerous medications and substances can produce false positive results in urine drug tests (see Graham et al. 2003, p. 338). Some researchers have compared quantitative versus qualitative testing, that is, testing to measure the amount and frequency of substance use versus testing to identify the presence or absence of a substance. Wolff and colleagues (1999) noted that false positive results can arise from incorrect identification of a drug or misinterpretation of a finding. Cone and Preston (2002) pointed out that EIA analysis lacks the specificity to distinguish among opioids, and Narcessian and Yoon (1997) reported a case in which consumption of a poppy seed bagel resulted in a positive urine EIA for morphine. Although EIA can produce some false positive results, TLC may be less sensitive than EIA, causing more false negative results (Verebey et al. 1998). In addition, laboratory and clerical errors and other problems cause inaccuracies. To check for any of the above problems, unexpected results should be discussed with the laboratory before they are conveyed to the patient.

Cone and Preston (2002) also addressed the pitfalls of qualitative testing, such as the increased possibility that with frequent testing a single drug use episode might trigger multiple positive test results (and result in consequences for the patient). In a comparative study, Preston and colleagues (1997) found that quantitative urine drug testing provided more information about patterns and frequency of cocaine use during treatment than qualitative testing. McCarthy (1994) similarly argued that quantifying the amount and frequency of drug use (including methadone) is more useful for treatment assessment and decisionmaking than qualitative analysis that simply identifies the presence or absence of a drug.

Responses to Test Results

Staff members should discuss drug test results with patients using a therapeutic, constructive approach. For example, staff members might express concern to patients over any tests that are positive for illicit drugs and seek additional information to explain these results. If a patient receives medication from a physician outside the OTP, staff should request informed consent to contact the physician and coordinate treatment, ask the patient to bring in prescription bottles, and record these prescriptions in patient records. OTP physicians should review prescriptions to determine whether and for how long their use is appropriate, particularly when medications have abuse potential.

Ultimately, if a positive drug test represents continuing drug use or a relapse after a period of abstinence, the counselor and patient should explore strategies to eliminate future use. Medication dosage and triggers to substance use should be examined, motivation for abstinence should be explored, and the patient should be taught skills to manage triggers and cravings. If drug tests continue to be positive, the medication dosage, amount of counseling, and number of OTP visits should be evaluated and may need adjustment. Furthermore, the patient might need the support provided by increasing counseling sessions and drug tests. These changes should be reflected in an updated treatment plan.

Medication Diversion

Since methadone treatment gained prominence in the late 1960s, concerns have existed about the diversion of medication from legitimate treatment use through theft, robbery, or patients or staff selling or giving away medication. SAMHSA-approved accrediting bodies pay particular attention to drug test results and whether an OTP appropriately monitors and follows up with patients who receive take-home medications (see chapter 5). The accrediting bodies require all OTPs to develop and implement a diversion control plan as part of their quality assurance program and to integrate the plan into both patient and staff orientations. The diversion control plan must contain specific measures to reduce the possibility of diversion and assign specific implementation responsibility to medical and administrative staff (see chapter 14).

Decisions About Take-Home Medication

Although drug test reports are a key factor in take-home medication decisions, OTPs should consider and document other considerations, such as employment and medical problems. Current Federal regulations (42 CFR, Part 8) outline eight criteria that the medical director of the OTP must consider when granting take-home privileges (see chapter 5). The physician also is required to reevaluate the appropriateness of take-home medications at least every 3 months.

Sometimes privileges are revoked simply to prevent possible medication diversion, without a concomitant programmatic response to address an unfavorable drug test report. When this occurs without discussion or explanation, OTPs create barriers between themselves and patients and appear to function more as monitoring and surveillance units than as treatment programs. If patients who are receiving take-home medications have positive drug test results, OTPs should consider such steps as a review of medication dosage and an increase if indicated, revision of the patient treatment plan, or an increase in the level of care, in addition to cessation or reduction in take-home doses.